The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016, in Bethesda, Maryland to assess the state of the field and to identify critical gaps in knowledge and areas of opportunity for research to advance the science of myocardial recovery with mechanical circulatory support (MCS) devices. The Working Group’s charge was to develop recommendations for the NHLBI which will advance the science of myocardial recovery with MCS to enhance its identification, realization, and long-term effectiveness as a therapeutic intervention. This scientific program will also likely yield advances in device technology and management that reduce MCS-associated adverse events that favorably impact myocardial recovery.
Cardiac remodeling driven by excess pressure and volume load drives the vicious cycle of progressive myocardial dysfunction in chronic heart failure (HF). By providing significant volume and pressure unloading and increased cardiac output, MCS devices allow a reversal of stress-related compensatory responses of the overloaded myocardium and, as a result, a subset of patients placed on long-term MCS can achieve variable degrees of improvement of the native heart structure/function and reversal of the systemic HF phenotype.
Members of the Working Group provided short summaries of critical gaps of knowledge in the field, including the genetic, molecular, cellular, physiologic, and engineering aspects of myocardial recovery. Working Group members outlined specific opportunities and challenges associated with current MCS devices with respect to device design and adverse events that impact myocardial recovery to stimulate hypothesis-driven novel basic, translational, and clinical investigations. Each session was followed by discussion and recommendations. A central point that emerged from these discussions was that the lessons we learn from the specific, tractable, and well-controlled MCS population (for whom we have access to serial function, tissue, and serum analyses) can and should be extrapolated to the broader HF population, especially the ability to identify and distinguish the molecular mechanisms that are associated with advanced heart failure that recovers structurally and functionally, from those associated with advanced heart failure that is end-stage and does not recover. These discoveries in this MCS population could lead to treatments and strategies applicable to all of the various stages and levels of severity of HF.
J. Timothy Baldwin, Ph.D., NHLBI, NIH
The working group provided the following recommendations and specific examples for each to the NHLBI regarding areas of need and opportunity in the science and engineering of myocardial recovery associated with MCS.
The Working Group recommended inclusion of adult and pediatric populations. The research efforts should, when appropriate, include patient-reported outcomes and cost data to allow study of the effect of interventions aimed at recovery on quality-of-life and cost-effectiveness.
The Working Group also developed the following working definition of cardiac recovery:
“A reversal of the pathological state of the myocardium with significant improvement in cardiac structure and function sufficient to achieve a sustained remission from the heart failure phenotype.”
A manuscript is planned for a peer-reviewed publication.